Chinese herb may yield drug for AIDS

GAITHERSBURG, Md. -- An experimental therapy with humble beginnings as a Chinese herbal remedy is generating excitement among researchers battling HIV when doctors are concerned about the ability of the virus to thwart drugs designed to fight it.

As the International AIDS Conference convenes next week, there are more than 20 drugs available to suppress the virus and at least 82 additional HIV therapies in development. But as quickly as drug companies find ways to sabotage HIV, the virus develops a new survival strategy. Nearly 30 percent of HIV-positive Americans have viral infections that were resistant to at least one drug in the multidrug cocktails that keep them alive.

``We desperately need new compounds with novel mechanisms of action," said Eric Freed, chief of the virus-cell interaction section of the HIV Drug Resistance Program of the National Cancer Institute.

That's why some patients, doctors, and researchers are excited about an experimental drug based on an herb known by the Latin name Syzigium claviflorum that had been used in Taiwan to treat diarrhea and stop bleeding. Now its derivative is being tapped to fight HIV by a small Watertown-based biotechnology company.

If approved by the Food and Drug Administration, bevirimat, developed by Panacos Pharmaceuticals Inc., would represent the first in a new class of drugs that uses an unusual approach to block maturation of the virus that causes AIDS.

The HIV virus can't make copies of itself; instead it hijacks a human cell to borrow its replication machinery. Bevirimat interrupts the process at a key stage, resulting in harmless, immature HIV copies that the body quickly flushes. The therapy is exciting, AIDS specialists say, even though it is at least three years from market, because it could offer a completely new tool to combat a 25-year-old foe.

And, bevirimat works later in the virus life cycle than protease inhibitors, which have been the mainstay of AIDS therapy. That hints at the opportunity to use bevirimat in potent combination with existing drugs, said Dr. Daniel R. Kuritzkes, director of AIDS research at Brigham and Women's Hospital and an associate professor of medicine at Harvard Medical School.

Bevirimat is being developed as physicians begin to use drugs from different classes in combination to fight the virus at different steps in its life cycle.

``We can, once again, get control of virus replication in patients with the most advanced disease who are resistant to other drugs and really have a major impact on the course of disease and on survival in these patients," said Kuritzkes, who is a paid consultant to Panacos.

Such new therapies could prove effective when given in combinations of specific classes.

``It's only when we started giving people three drugs from at least two different classes that we really started making an impact," said Kenneth Mayer, medical research director at Boston's Fenway Community Health and a Brown University professor of medicine.

In 2003, roughly 1.2 million Americans lived with acquired immune deficiency syndrome, and another estimated 40,000 Americans are newly infected with the human immunodeficiency virus each year, according to the Centers for Disease Control and Prevention.

But therapies have been improving steadily. By the calculations of researchers at Massachusetts General Hospital and Harvard Medical School, people who started AIDS therapy in 2003 lived an estimated 13 years longer than people diagnosed with AIDS in 1988.

Experimental AIDS therapies in clinical trial or awaiting FDA approval hint at more life-saving benefits, like the once-a-day AIDS pill that the agency hailed last month as the ``holy grail" of drug development because it simplifies drug delivery in developing nations. The experimental therapies include drugs that bolster the body's ability to block the doorways that HIV uses to enter cells, that enhance the body's ability to neutralize the virus, and that limit the damage caused by HIV infection.

Panacos estimates its drug could garner $500,000 to $1 billion in peak annual sales from a drug candidate initially spotted by a professor at the University of North Carolina at Chapel Hill who was screening natural products in search of potential HIV therapies.

``There aren't many new mechanism drugs," Graham P. Allaway, Panacos president, said during an interview at the company's research-and-development facility here. ``So far, it looks potent, and it has a great safety profile."

In June, bevirimat entered a crucial, multicenter clinical trial that tests escalating doses of the drug in combination with antiretroviral therapy. If all goes well, the trial could enroll up to 144 patients.

``The proof of the pudding is always what happens when you give it to people and look at what the potency of the antiviral effect is," said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health. ``Preliminary results actually indicated that there is the effect that you'd be interested in."

Diedtra Henderson can be reached at dhenderson@globe.com.